Cyclin-dependent kinase 5-deficient mice demonstrate novel developmental arrest in cerebral cortex

Edward C. Gilmore, Toshio Ohshima, André M. Goffinet, Ashok B. Kulkarni, Karl Herrup

Research output: Contribution to journalArticle

261 Citations (Scopus)

Abstract

The cerebral cortex of mice with a targeted disruption in the gene for cyclin-dependent kinase 5 (cdk5) is abnormal in its structure. Bromodeoxyuridine labeling reveals that the normal inside-out neurogenic gradient is inverted in the mutants; earlier born neurons are most often found superficial to those born later. Despite this, the early preplate layer separates correctly and neurons with a normal, pyramidal morphology can be found between true marginal zone and subplate. Consistent with their identity as layer VI corticothalamic neurons, they can be labeled by Dil injections into thalamus. The Dil injections also reveal that the trajectories of the cdk5(-/-) thalamocortical axons are oblique and cut across the entire cortical plate, instead of being oriented tangentially in the subcortical white matter. We propose a model in which the cdk5(-/-) defect blocks cortical development at a heretofore undescribed intermediate stage, after the splitting of the preplate, but before the migration of the full complement of cortical neurons.

Original languageEnglish
Pages (from-to)6370-6377
Number of pages8
JournalJournal of Neuroscience
Volume18
Issue number16
DOIs
Publication statusPublished - 1998 Aug 15

Keywords

  • BrdU
  • Cdk5
  • Cerebral cortical development
  • Neuronal migration
  • Neuronal morphology
  • Reeler

ASJC Scopus subject areas

  • Neuroscience(all)

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